Boron rich nanotube drug carrier system is suited for boron neutron capture therapy

Abstract Boron neutron capture therapy (BNCT) is a two-step therapeutic process that utilizes Boron-10 in combination with low energy neutrons to effectively eliminate targeted cells. This therapy is primarily used for difficult to treat head and neck carcinomas; recent advances have expanded this m...

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Autores principales:	Fabian Heide, Matthew McDougall, Candice Harder-Viddal, Roy Roshko, David Davidson, Jiandong Wu, Camila Aprosoff, Aniel Moya-Torres, Francis Lin, Jörg Stetefeld
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d1a8ba6943f14b2d81e7448fdac0e9ec
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spelling	oai:doaj.org-article:d1a8ba6943f14b2d81e7448fdac0e9ec2021-12-02T16:06:44ZBoron rich nanotube drug carrier system is suited for boron neutron capture therapy10.1038/s41598-021-95044-02045-2322https://doaj.org/article/d1a8ba6943f14b2d81e7448fdac0e9ec2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95044-0https://doaj.org/toc/2045-2322Abstract Boron neutron capture therapy (BNCT) is a two-step therapeutic process that utilizes Boron-10 in combination with low energy neutrons to effectively eliminate targeted cells. This therapy is primarily used for difficult to treat head and neck carcinomas; recent advances have expanded this method to cover a broader range of carcinomas. However, it still remains an unconventional therapy where one of the barriers for widespread adoption is the adequate delivery of Boron-10 to target cells. In an effort to address this issue, we examined a unique nanoparticle drug delivery system based on a highly stable and modular proteinaceous nanotube. Initially, we confirmed and structurally analyzed ortho-carborane binding into the cavities of the nanotube. The high ratio of Boron to proteinaceous mass and excellent thermal stability suggest the nanotube system as a suitable candidate for drug delivery into cancer cells. The full physicochemical characterization of the nanotube then allowed for further mechanistic molecular dynamic studies of the ortho-carborane uptake and calculations of corresponding energy profiles. Visualization of the binding event highlighted the protein dynamics and the importance of the interhelical channel formation to allow movement of the boron cluster into the nanotube. Additionally, cell assays showed that the nanotube can penetrate outer membranes of cancer cells followed by localization around the cells’ nuclei. This work uses an integrative approach combining experimental data from structural, molecular dynamics simulations and biological experiments to thoroughly present an alternative drug delivery device for BNCT which offers additional benefits over current delivery methods.Fabian HeideMatthew McDougallCandice Harder-ViddalRoy RoshkoDavid DavidsonJiandong WuCamila AprosoffAniel Moya-TorresFrancis LinJörg StetefeldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fabian Heide Matthew McDougall Candice Harder-Viddal Roy Roshko David Davidson Jiandong Wu Camila Aprosoff Aniel Moya-Torres Francis Lin Jörg Stetefeld Boron rich nanotube drug carrier system is suited for boron neutron capture therapy
description	Abstract Boron neutron capture therapy (BNCT) is a two-step therapeutic process that utilizes Boron-10 in combination with low energy neutrons to effectively eliminate targeted cells. This therapy is primarily used for difficult to treat head and neck carcinomas; recent advances have expanded this method to cover a broader range of carcinomas. However, it still remains an unconventional therapy where one of the barriers for widespread adoption is the adequate delivery of Boron-10 to target cells. In an effort to address this issue, we examined a unique nanoparticle drug delivery system based on a highly stable and modular proteinaceous nanotube. Initially, we confirmed and structurally analyzed ortho-carborane binding into the cavities of the nanotube. The high ratio of Boron to proteinaceous mass and excellent thermal stability suggest the nanotube system as a suitable candidate for drug delivery into cancer cells. The full physicochemical characterization of the nanotube then allowed for further mechanistic molecular dynamic studies of the ortho-carborane uptake and calculations of corresponding energy profiles. Visualization of the binding event highlighted the protein dynamics and the importance of the interhelical channel formation to allow movement of the boron cluster into the nanotube. Additionally, cell assays showed that the nanotube can penetrate outer membranes of cancer cells followed by localization around the cells’ nuclei. This work uses an integrative approach combining experimental data from structural, molecular dynamics simulations and biological experiments to thoroughly present an alternative drug delivery device for BNCT which offers additional benefits over current delivery methods.
format	article
author	Fabian Heide Matthew McDougall Candice Harder-Viddal Roy Roshko David Davidson Jiandong Wu Camila Aprosoff Aniel Moya-Torres Francis Lin Jörg Stetefeld
author_facet	Fabian Heide Matthew McDougall Candice Harder-Viddal Roy Roshko David Davidson Jiandong Wu Camila Aprosoff Aniel Moya-Torres Francis Lin Jörg Stetefeld
author_sort	Fabian Heide
title	Boron rich nanotube drug carrier system is suited for boron neutron capture therapy
title_short	Boron rich nanotube drug carrier system is suited for boron neutron capture therapy
title_full	Boron rich nanotube drug carrier system is suited for boron neutron capture therapy
title_fullStr	Boron rich nanotube drug carrier system is suited for boron neutron capture therapy
title_full_unstemmed	Boron rich nanotube drug carrier system is suited for boron neutron capture therapy
title_sort	boron rich nanotube drug carrier system is suited for boron neutron capture therapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d1a8ba6943f14b2d81e7448fdac0e9ec
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Boron rich nanotube drug carrier system is suited for boron neutron capture therapy

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